Hyperprolactinaemia Amenorrhoea Galactorrhoea Loss of libido Infertility

Endocrine System II (b) Flashcards by Elyaa Saleh

Celluar Components of the Adeno-Hypophysis (Anterior pituitary)

basophilic, eosinophilic and
chromophobic cytoplasm

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Anterior Pituitary (Adeno-Hypophysis) produces?

PRL, GH,
ACTH, FSH, LH and TSH

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Celluar Components of the Posterior Pituitary (Neuro-Hypophysis)

modified glial cells (pituicytes) and axonal
processes from Hypothalamus

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Posterior Pituitary (Neuro-Hypophysis) produces?

Oxytocin and ADH (or Vasopressin)

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loc of the pituitary gland

Base of the brain, within Sella turcica
(bellow the hypotahlamus connected by a stalk-composed of axons)

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Cause of Hyperpituitarism

*Excessive secretion of trophic hormones

Anterior Pituitary Aden.

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Cause of Hypopituitarism

* Deficiency of trophic hormones

Ischaemic injury, surgery, radiation, inflammatory reactions, Non-functional Pituitary Adenomas (through compression of adjacent normal tissue)

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Complictions of Pituitary Adenoma

i. Visual field defects (bitemporal hemianopsia),
ii. Elevated intra-cranial pressure (headache, nausea, vomiting),
iii. Seizures or obstructive hydrocephalus
iv. Pituitary apoplexy (acute haemorrhage in an Adenoma)

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Causes of Hyperpituitarism
& Pituitary Adenomas

Anterior Pituitary Adenoma (most common)
Hyperplasia
Pituitary Carcinoma
Secretion of hormones by extra-pituitary tumour

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patho of Hyperpituitarism
& Pituitary Adenomas

*GNASI gene mutations (a-subunit of Gs protein)
–> Persistent generation of cAMP –> Unchecked cellular proliferation;
About 40% of GH-secreting Somatotroph Cell Adenomas

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Genes involved in the development of familial Pituitary Adenomas (Prolactinoma)?

MEN 1, CDKNIB, PRKARIA
and AIP

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* Familial Pituitary Adenomas

Mutations of ——– gene are associated with an
aggressive behaviour , such as invasion and
recurrence

TP53

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Microscopic Findings:
* Uniform, polygonal cells arranged in sheets, cords or papillae
* Uniform or pleomorphic nuclei (Monomorphic
appearance of tumour cells)
* Low mitotic index
* Acidophilic, basophilic or chromophobic cytoplasm
* Sparse supporting connective tissue or reticulin
* Small round cells
* Small round nuclei
* Pink to blue cytoplasm

PITUITARY ADENOMAS (Anterior)

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Epi of Prolactinomas

Most common type of functional
Pituitary Adenomas

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CF of Prolactinomas

Hyperprolactinaemia
Amenorrhoea
Galactorrhoea
Loss of libido
Infertility

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What is Pituitary Stalk effect ?

Hyperprolactinaemia caused by a mass
(other than Prolactinoma) in the supra-sellar
compartment –> which inhibits the normal inhibitory influence of Hypothalamus on Prolactin secretion

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Microscopic features:
* Chromophobic cells (clear cells)
* Sphaerical microcalcifications

Prolactinomas

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Epi of Growth Hormone-Producing
(Somatotroph) Adenomas

Second most common type of
functional Pituitary Adenomas

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Microscopic features:
* Densely or sparsely granulated cells
* Paranuclear “fibrous body”

Growth Hormone-Producing (Somatotroph) Adenomas

*Paranuclear bodies = indication of Pituitary adenomas

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* GH-Producing (Somatotroph) Adenomas

Overproduction and release of GH leads to hepatic
secretion of —— –>
–> In cases of prepubertal children (before closure of epiphyses) —-> —————–
–> After closure of epiphyses –> ————–

secretion of IGF-1
Before –> Giganitism
After (adults) –> Acromegaly

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CF of Growth Hormone-Producing
(Somatotroph) Adenomas

Gigantism or Acromegaly
Abnormal Glucose tolerance
Diabetes Mellitus
Generalised muscle weakness
Hypertension
Arthritis
Osteoporosis
Congestive Heart Failure

Epi of ACTH-Producing Adenomas

Commonly, Micro-Adenomas
Clinically silent or manifested as Cushing Syndrome

Cause of Nelson Syndrome

Development of large (Macro-adenomas), aggressive ACTH Adenomas, after removal of both Adrenal Glands,
for treatment of Cushing Syndrome

Absence of Adrenal Glands –> {No/yes} Hypercortisolism

CF of Nelson Syndrome

**i. Hyperpigmentation of the skin**, ii. Headaches and iii. Vision impairment

Lab findings of Nelson Syndrome

**↑** levels of **ACTH** and **β-MSH**

CF of Gonadotroph (FSH- and LH-producing) Adenomas

* Impaired vision, * headaches, * **diplopia** (double vision), * pituitary apoplexy

Immunohistochemistry of **Gonadotroph** (FSH- and LH-producing) **Adenomas**

**+ve** for : **common Gonadotropin α-subunit** , the specific **β-FSH** and **β-LH** subunits

Epi of **Thyrotroph** (TSH-producing) **Adenomas**

* 1% of Anterior Pituitary Adenomas * **Rare cause of Hyperthyroidism**

Epi of Non-functional Pituitary Adenomas

25% of all pituitary tumours (posterior)

CF of Non-functional Pituitary Adenomas

* Typical presentation of mass effects * Compromise of the residual Anterior Pituitary --> **Hypopituitarism**

Epi of Pituitary Carcinomas

Rare occurrence

Microscopic features:  **Rosettes of small cells**  **Monomorphic (pleomorphic) chromatin-rich nuclei**

Null-Cell Adenomas (aka Hormone-negative adenomas) | *Null-cell adenomas have abscense of immuno-histochemical reactivity

------------ : Hypofunction of the Anterior Pituitary, after loss or absence of >75% of the Anterior Pituitary parenchyma

Hypopituitarism

Causes of Hypopituitarism

1) Hypopituitarism, **accompanied by Diabetes Insipidus**, is almost always of hypothalamic origin 2) **Non-functioning Pituitary Adenomas** 3) Ablation of the Pituitary Gland by **surgery or irradiation** 4) Inflammatory disorders (e.g. **Sarcoidosis**, Tbc), 5) trauma and metastatic neoplasms 6) **Sheehan's syndroms or postpartum necrosis** of Anterior Pituitary Gland 7) Other causes of ischaemic necrosis: DIC, sickle cell anaemia, trauma, shock, etc.

CF of Hypopituitarism (depending on hormone(s) lacking) * **GH-deficiency** --> **-----** * **GnRH deficiency** --> **------- (F); ------ (M)** * **PRL deficiency** --> **----------** * **TSH deficiency** --> **--------** * **ACTH deficiency** --> **---------**

* **GH-deficiency** --> Dwarfism (in children) * **GnRH deficiency**--> Amenorrhoea and Infertility (F); Decreased Libido and Impotence (M) * **PRL deficiency** --> Failure of postpartum Lactation * **TSH deficiency** --> Hypo-Thyroidism * **ACTH deficiency** --> Hypo-Adrenalism | *GnRH: Gonadotropin-Releasing Hormone

causes of Empty sella Turcica

* Pituitary compression through herniation of the Arachnoidea (Arachnoid mater) * **Sheehan syndrome** * Total infarction of an Adenoma * Operation or Radiation of the Hypophysis

Posterior Pituitary Syndromes examples

1) Central Diabetes Insipidus 2) Syndrome of Inappropriate ADH (SIADH) secretion

# * Posterior Pituitary Syndromes Causes of Syndrome of Inappropriate ADH (SIADH) secretion

* Ectopic ADH secretion, by a malignant neoplasm (e.g. SCLC) * Non-neoplastic diseases of the lung * Local injury to the Hypothalamus or Neuro-Hypophysis

# * Posterior Pituitary Syndromes patho of Syndrome of Inappropriate ADH (SIADH) secretion

Resorption (loss) of excessive amounts of free water --> Hyponatraemia (low Na+)

# * Posterior Pituitary Syndromes CF of Syndrome of Inappropriate ADH (SIADH) secretion

* Cerebral oedema --> Neurologic dysfunction * Normal blood volume and NO peripheral oedema

# * Posterior Pituitary Syndromes Cause of Central Diabetes Insipidus

* Idiopathic * Head trauma * Neoplasms * Inflammatory disorders

# * Posterior Pituitary Syndromes Lab findings of Central Diabetes Insipidus

**Increased serum Sodium and osmolality**, as a result of excessive renal loss of free H2O

# * Posterior Pituitary Syndromes Cf of Central Diabetes Insipidus

* **Polyuria** (dilute urine, with low specific gravity) * **Polydipsia**

MoI of MEN-1 + mutation

MoI: AD Mutation: inactivation of both alleles of the MEN-1 gene

MEN-1 loc+ examples

* 1) parathyroid --> **Primary Hyperparathyroidism, due to Hyperplasia or Adenoma**; Most common manifestation in MEN-1 (**80-95% of cases**) 2) Pituitary --> **Prolactinoma** (Prolactin-secreting Macroadenoma) 3) Pancrease --> *insulinomas** (zollinger Elison syndrome)

MEN-2 moI+MUTATION

MoI: AD Mutation: germ-line RET mutations, activating mutations of the RET proto-oncogene

# MEN-2 All persons with germ-line RET mutations should undergo **prophylactic thyroidectomy** to prevent the unavoidable development of ?

**Medullary Carcinomas**

Loc of MEN-2A +examples

1) Thyroid: **Medullary Carcinomas** 2) Adrenal Medulla --> **Pheochromocytomas**; 3) Parathyroid: 10-20% of patients --> Development of **Parathyroid Gland Hyperplasia** --> **Primary Hyperparathyroidism**

Endocrine Manifestations in MEN-1

* Zollinger-Ellison Syndrome associated with Gastrinomas * Hypoglycaemia associated with Insulinomas

MEN-2B involves?

**Thyroid (Medullary carcinoma) and the Adrenal Medulla (pheochromocytoma)** Thyroid and Adrenal Medulla disease shows similarities to MEN-2A, with the following differences: * **MEN-2B patients do not develop Primary Hyperparathyroidism** * Extra-endocrine manifestations in MEN-2B patients: * **Ganglio-Neuromas of mucosal sites (GI tract, lips, tongue)** * **Marfanoid habitus**